Jason M. Ashford

Attention and Working Memory Abilities in Children Treated for Acute Lymphoblastic Leukemia

To extend investigation beyond global cognitive measures prevalent in the literature, this study examined attention and working memory (WM) abilities of survivors of childhood acute lymphoblastic leukemia (ALL), the separate contributions of attention and WM to intelligence quotient (IQ), and their association with neuroimaging changes.

Working memory performance among childhood brain tumor survivors.

While longitudinal studies of children treated for brain tumors have consistently revealed declines on measures of intellectual functioning, greater specification of cognitive changes following treatment is imperative for isolating vulnerable neural systems and developing targeted interventions. Accordingly, this cross-sectional study evaluated the performance of childhood brain tumor survivors (n = 50) treated with conformal radiation therapy, solid tumor survivors (n = 40) who had not received central nervous system (CNS) -directed therapy, and healthy sibling controls (n = 40) on measures of working memory [Digit Span and computerized self-ordered search (SOS) tasks]. Findings revealed childhood brain tumor survivors were impaired on both traditional [Digit Span Backward- F(2,127) = 5.98; p < .01] and experimental [SOS-Verbal- F(2,124) = 4.18; p < .05; SOS-Object- F(2,126) = 5.29; p < .01] measures of working memory, and performance on working memory measures correlated with intellectual functioning (Digit Span Backward- r = .45; p < .0001; SOS- r = -.32 to -.26; p < .01). Comparison of performance on working memory tasks to recognition memory tasks (computerized delayed match-to-sample) offered some support for greater working memory impairment. This pattern of findings is consistent with vulnerability in functional networks that include prefrontal brain regions and has implications for the clinical management of children with brain tumors.

Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers.

In children, CNS‐directed cancer therapy is thought to result in decreased cerebral white matter volumes (WMV) and subsequent neurocognitive deficits. This study was designed as a prospective validation of the purported reduction in WMV, associated influential factors, and its relationship to neurocognitive deficits in a very large cohort of both acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) survivors in comparison to an age similar cohort of healthy sibling controls.

The impact of attention on social functioning in survivors of pediatric acute lymphoblastic leukemia and brain tumors

The cognitive late effects experienced by many survivors of pediatric acute lymphoblastic leukemia (ALL) and brain tumors are well‐established. The most commonly reported deficit is difficulty with attention. Problems with social functioning have also been identified, but their relationship with cognitive functioning is not well understood. This multi‐site, cross‐sectional study aimed to examine the impact of attention on social functioning.

The Utility of Parent Report in the Assessment of Working Memory among Childhood Brain Tumor Survivors

Childhood brain tumor survivors are at increased risk for neurocognitive impairments, including working memory (WM) problems. WM is typically assessed using performance measures. Little is known about the value of parent ratings for identifying WM difficulties, the relationship between rater and performance measures, or predictors of parent-reported WM problems in this population. Accordingly, the current study examined the utility of parent report in detecting WM difficulties among childhood brain tumor survivors treated with conformal radiation therapy (n = 50) relative to siblings (n = 40) and solid tumor survivors not receiving central nervous system-directed therapy (n = 40). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants were administered WM measures (digit span, self-ordered search tasks). Findings revealed parents rated brain tumor survivors as having significantly more WM problems (p < .01) compared to controls. However, the BRIEF-WM scale demonstrated poor sensitivity and specificity for detecting performance-based problems. Significant, albeit modest, correlations were found between the BRIEF-WM scale and performance measures (r = -.24-.22; p < .05) for the combined group. Age at testing, socioeconomic status, and IQ were significant predictors of parent reported WM problems. Rater and performance measures offer complimentary yet different information in assessing WM, which reiterates the importance of using both within the context of clinical assessment.

Predictors of non-participation in a randomized intervention trial to reduce environmental tobacco smoke (ETS) exposure in pediatric cancer patients.

Exposure to environmental tobacco smoke (ETS) is associated with the development of serious health consequences in children with cancer due to preexisting disease and treatment‐related vulnerabilities. The purpose of the current investigation was to identify predictors of non‐participation in a randomized intervention trial to reduce ETS exposure among pediatric cancer patients.

Clinical Utility of the N-back Task in Functional Neuroimaging Studies of Working Memory

Introduction: N-back tasks are commonly used in functional neuroimaging studies to identify the neural mechanisms supporting working memory (WM). Despite widespread use, the clinical utility of these tasks is not well specified. This study compared N-back performance during functional magnetic resonance imaging (fMRI) with task data acquired outside of the scanner as a measure of reliability across environment. N-back task validity was examined in relation to performance and rater-based measures used clinically to assess working memory. Method: Forty-three healthy adults completed verbal and object N-back tasks during fMRI scanning and outside the scanner. Task difficulty was varied parametrically (0, 1, and 2-back conditions). Order of N-back task completion was stratified by modality (verbal/object) and environment. Participants completed the Digit Span (DS) and provided self-ratings using the Behavior Rating Inventory of Executive Function (BRIEF-WM). Results: Mean verbal and object N-back accuracy was above 95% across load conditions; task difficulty was effectively manipulated across load conditions. Performance accuracy did not significantly differ by environment. N-back reaction time was slower during fMRI (F = 6.52, p = .01, ηp2 = .13); participants were faster when initially completing tasks outside the scanner (ηp2 = .10–.15). Verbal 2-back accuracy was significantly related to DS performance (r = .36, p = .02). N-back performance was not related to BRIEF-WM. Conclusions: Our results provide evidence for reliability of N-back accuracy during fMRI scanning; however, reliability of reaction time data is affected by order of task presentation. Data regarding construct validity are inconsistent and emphasize the need to consider clinical utility of behavioral measures in the design and interpretation of functional neuroimaging studies.

Long-Term Efficacy of Computerized Cognitive Training Among Survivors of Childhood Cancer: A Single-Blind Randomized Controlled Trial

Objective To investigate the long‐term efficacy of computerized cognitive training in improving cognitive outcomes among childhood cancer survivors. Methods Sixty‐eight survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) were randomly assigned to computerized cognitive intervention (23 ALL/11 BT, age = 12.21 ± 2.47) or a waitlist control group (24 ALL/10 BT, age = 11.82 ± 2.42). Cognitive assessments were completed pre‐, immediately post‐, and 6 months postintervention. Results A prior report showed training led to immediate improvement in working memory, attention and processing speed. In the current study, piecewise linear mixed effects modeling revealed that working memory and processing speed were unchanged from immediate to 6 months postintervention (intervention &bgr; = −.04 to .01, p = .26 to .95; control &bgr; = −.06 to .01, p = .23‐.97), but group differences on an attention measure did not persist. Conclusion Cognitive benefits are maintained 6 months following computerized cognitive training, adding to potential clinical utility of this intervention approach.

Investigating the relationship between COMT polymorphisms and working memory performance among childhood brain tumor survivors

Survivors of childhood brain tumors are at increased risk for neurocognitive impairments, including deficits in abilities supported by frontal brain regions. Catechol‐O‐methyltransferase (COMT) metabolizes dopamine in the prefrontal cortex, with the Met allele resulting in greater dopamine availability and better performance on frontally mediated tasks compared to the Val allele. Given the importance of identifying resiliency factors against the emergence of cognitive late effects, the current study examined the relationship between COMT genotype and working memory performance among childhood brain tumor survivors.

Neurocognitive functioning in pediatric craniopharyngioma: performance before treatment with proton therapy

The goal of this study was to investigate the impact of patient-, disease-, and treatment-related variables upon neurocognitive outcomes in pediatric patients with craniopharyngioma prior to treatment with proton therapy or observation after radical resection. For all participants (N = 104), relevant clinical and demographic variables were attained and neurocognitive evaluations completed prior to irradiation or planned observation. One-sample t-tests were conducted to compare performance to published normative data. Linear models were used to investigate predictors of performance on measures where performance was below normative expectations. Participants showed poorer performance in comparison to the normative group across neurocognitive domains including executive functions (e.g., working memory; Wechsler Digit Span Backward p = 0.03), learning and memory (e.g., California Verbal Learning Test [CVLT] Total T p = 0.00), and fine-motor coordination (e.g., Grooved Pegboard Dominant Hand p = 0.00). Poor performance across areas was predicted by presurgical hypothalamic involvement (e.g., Behavior Rating Inventory of Executive Function Working Memory Index Grade 2 β = −7.68, p = 0.03; CVLT Total T Grade 2 β = 7.94, p = 0.04; Grade 3 β = −9.80, p = 0.00), extent of surgery (e.g., CVLT Total T Resection β = −7.77, p = 0.04; Grooved Pegboard Dominant Hand β = −1.58, p = 0.04), and vision status (e.g., CVLT Total T Reduced vision without impairment β = −10.01, p = 0.02; Grooved Pegboard Dominant Hand Bilateral field defect β = −1.45, p = 0.01; Reduced vision without impairment β = −2.30, p = 0.00). This study demonstrated that patients with craniopharyngioma show weaker neurocognitive performance in comparison to the normative population resulting from tumor, events leading to diagnosis, and early surgical intervention. Systematic investigation of neurocognitive performance before treatment with radiation therapy is essential to evaluating the potential risks and benefits of newer methods of radiation therapy including proton therapy.